Treatment Protocol
Evidence Matrix

While the BAT PILL™ protocol is grounded in a century of brain science, the direct scientific journey begins with the discovery of rapamycin in the 1960s and the subsequent understanding of mTOR’s role in aging and neurodegeneration. The following evidence scan highlights pivotal studies,  curated by era, that shaped the therapeutic foundation of the BAT Pill protocol. For earlier foundational work in Alzheimer’s biomarkers and diagnosis, see our BAT TESTING™ Evidence Scan. All studies are selected and summarized by the BATWatch clinical science team using our proprietary Evidence Matrix (see Research & Reference Policy for methods).

Scan History

1960 – 2000 Evidence Scan

Over 1,800 studies on rapamycin, sirolimus, and mTOR signaling were published between 1960 and 2000. This era laid the groundwork for the BAT PILL™ protocol, with breakthroughs revealing how rapamycin and mTOR control cellular cleanup (autophagy) and the removal of potentially harmful proteins. These discoveries paved the way for targeted strategies to support brain health and address biological drift.

Vezina, C., Kudelski, A., Sehgal, S. N. (1975): Discovery of rapamycin: This paper reports the original isolation of rapamycin (sirolimus) from soil samples collected on Easter Island, opening a new era in immunology and cellular signaling. View Study

Brown, E. J., Albers, M. W., Bumsted, K. M., et al. (1994): Discovery of mTOR: Identified the mammalian target of rapamycin (mTOR) as the cellular receptor for rapamycin, revolutionizing our understanding of cell growth, nutrient sensing, and aging. View Study

Sabatini, D. M., Erdjument-Bromage, H., Lui, M., et al. (1994): mTOR’s molecular identity: Provided detailed molecular characterization of mTOR, clarifying its central role in the action of rapamycin and setting the stage for targeted interventions in aging and neurodegeneration. View Study

Noda, T., & Ohsumi, Y. (1998): Rapamycin induces autophagy: This landmark study directly demonstrated that rapamycin induces autophagy in yeast by inhibiting TOR, providing a mechanistic foundation for rapamycin’s potential in enhancing cellular cleanup, relevant for neurodegenerative disease clearance. View Study

…1,888 more

2001 – 2010 Evidence Scan

Over 12,500 studies on Alzheimer’s disease and related neurodegeneration were published between 2001 and 2010. This era includes groundbreaking work on the mechanisms behind beta-amyloid and tau accumulation, as well as the first pivotal studies showing that rapamycin and mTOR inhibition could drive cellular cleanup (autophagy) and reduce toxic protein buildup in the brain. The decade set the stage for BAT-targeted interventions, laying a foundation for the BAT PILL™ protocol’s unique approach to brain health.

Harrison, D. E., Strong, R., Sharp, Z. D., et al. (2009): Although best known for longevity, this multi-site mouse study included data showing rapamycin’s effect on age-associated pathologies, including neurodegeneration, helping cement mTOR as a key target in age-related brain protein accumulation. View Study

Spilman, P., Podlutskaya, N., Hart, M. J., et al. (2010): Showed that inhibiting mTOR with rapamycin not only decreased amyloid-β levels and plaque burden, but also improved learning and memory in a mouse AD model, providing a mechanistic basis for BAT clearance and functional benefit. View Study

Fagan, A. M., Roe, C. M., Xiong, C., et al. (2007): Demonstrated that low CSF Aβ42 is associated with amyloid PET positivity and future cognitive decline, linking CSF biomarker changes with brain imaging and clinical outcomes. View Study

Caccamo, A., Majumder, S., Richardson, A., et al. (2010): Demonstrated that rapamycin treatment reduced both beta-amyloid plaques and tau pathology in transgenic Alzheimer’s disease mice, showing simultaneous impact on BAT levels through mTOR inhibition. View Study

…12,520 more

2011 – 2019 Evidence Scan

Over 31,800 studies on Alzheimer’s disease, mTOR signaling, autophagy, and neurodegeneration were published between 2011 and 2020. This era marked a turning point: animal and translational research confirmed that rapamycin and related treatments could clear beta-amyloid and tau, restore brain and vascular function, and target the biological roots of neurodegenerative drift. These discoveries firmly established the scientific core of the BAT PILL™ protocol and paved the way for human clinical exploration.

Majumder, S., et al. (2011): This landmark animal study showed that giving rapamycin before amyloid plaques and tau tangles formed could activate autophagy, clear toxic brain proteins, and actually prevent memory problems, highlighting the importance of early, biological intervention. View Study

Lin, A. L., et al. (2013): Researchers found that chronic rapamycin restored blood vessel function and improved memory in mouse models of Alzheimer’s, providing real-world evidence that mTOR inhibition benefits both brain health and vascular integrity. View Study

Tang, Z., et al. (2013): This study unraveled how mTOR signaling drives tau protein imbalance in the brain and demonstrated that rapamycin can restore tau homeostasis, supporting its use for tau clearance in neurodegenerative disease. View Study

Martinez-Vicente, M. (2015): A comprehensive review that summarizes the latest science on autophagy in neurodegenerative diseases, highlighting how rapamycin and related treatments can restore the brain’s natural cleanup systems and target toxic protein buildup. View Study

…31,808 more

2020 – 2024 Evidence Scan

Over 16,000 studies on Alzheimer’s disease, autophagy, and mTOR-based interventions were published between 2021 and 2024. This era represents a true turning point in brain health: for the first time, real-world outcomes from the BATWATCH™ Protocol have moved biomarker-driven prevention out of theory and into everyday clinical use. Leveraging rapid advances in mTOR science and digital tracking, we initiated a rolling observational study tracking biological drift in Beta-Amyloid (BA) 42/40 and pTau 181 levels across hundreds of BAT PILL™ cycles.

And the result was large-scale, patient-level data now revealing that most individuals, regardless of baseline risk, can achieve meaningful reductions in key biomarkers through short-term intervention. The field has shifted from static measurement to real-time risk reversal, ushering in a new era of actionable brain health science.

BATWatch RWE Study (Internal Data, 2024-ongoing): Ongoing prospective observational data collection from >600 participants in the BATWatch Protocol, tracking BA 42/40 and pTau 181 before and after BAT Pill cycles. Interim analyses as of 2024 show up to 87% of patients reduced BA 42/40 and up to 74% decreased pTau 181, with ongoing updates planned as the cohort expands. Interim data reported May 2025; study remains in active enrollment and follow-up.

Benito-Cuesta, I., et al. (2021): This experimental study demonstrated that while AMPK activation failed to enhance autophagy in neurons, mTORC1 inhibition (the mechanism of rapamycin) led to significant beta-amyloid clearance, directly supporting the core mechanism of the BAT Pill protocol. View Study

Silva, M. C., et al. (2020): This study found that pharmacological activation of autophagy, including rapamycin, prolonged tau clearance and rescued neurons from stress in tauopathy models—reinforcing mTOR modulation as a disease-modifying strategy. View Study

Carosi, J. M., et al. (2023): A comprehensive review proposing rapamycin as a promising candidate for the treatment of neurodegenerative disease, synthesizing the latest findings on mTOR inhibition, autophagy, and protein clearance in Alzheimer’s models. View Study

…16,142 more

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